Comorbid depression and sleep behaviour disorder puts patients and relatives at risk of neurodegeneration

Comorbid major depressive disorder and rapid eye movement sleep behaviour disorder (MDD-RBD) is a common subtype of MDD. These patients and their first-degree relatives (FDRs) are at risk of neurodegeneration, researchers from the Chinese University of Hong Kong (CUHK) have reported.

RBD is a parasomnia characterized by dream-enactment behaviours that emerge during rapid eye movement sleep, and is one of the earliest prodromal markers of Parkinson’s disease. MDD is a risk factor of neurodegeneration. [Neurology 2015;84:24; PLoS Med 2020:17;e1003016]

Comorbid psychiatric disorders and RBD (psy-RBD) is common, especially in the MDD population. In Hong Kong, RBD is present in 8.77 percent of patients with MDD – a prevalence nearly 10 times higher than that in the general population. MDD-RBD is associated with higher levels of prodromal neurodegenerative markers, such as colour vision deficit and olfactory dysfunction, vs MDD without RBD. [J Neurol Neurosurg Psychiatry 2022;93:1010-1017]

“It is unclear whether psy-RBD is secondary to antidepressant use or an independent diagnostic entity that heralds underlying neurodegeneration,” noted Dr Jing Wang of the Department of Psychiatry, CUHK.  [J Neurol Neurosurg Psychiatry 2023;doi:10.1136/jnnp-2022-330922]

To better understand the relationship between neurodegeneration and psy-RBD, the researchers conducted a case-control family study that compared risks of α-synucleinopathy spectrum features (ie, possible RBD, neurodegenerative prodromal markers, and clinical diagnoses of neurodegenerative disorders) in FDRs of three groups of probands, including psy-RBD-FDRs (n=583), psychiatric controls (n=361), and healthy controls (n=427). “MDD was the most frequent psychiatric diagnosis in probands of psy-RBD-FDRs and psychiatric controls [both >90 percent],” pointed out Wang.

Psy-RBD-FDRs had higher risks of possible RBD vs psychiatric controls (adjusted hazard ratio [aHR], 2.26; 95 percent confidence interval [CI], 1.25–4.08) and healthy controls (aHR, 2.02; 95 percent CI, 1.17–3.56), suggesting that RBD symptoms aggregate in psy-RBD families.

Additionally, risk of Parkinson’s disease or dementia was significantly higher in psy-RBD-FDRs vs psychiatric controls (aHR, 3.91; 95 percent CI, 1.27–11.99) and healthy controls (aHR, 5.5; 95 percent CI, 1.89–16.07), indicating a higher risk of neurodegeneration in FDRs of psy-RBD patients.

“Results of the family study prove that MDD-RBD is not simply a drug-induced phenomenon, but is associated with underlying neurodegeneration,” said Wang. “The absence of confirmed neurodegeneration risk in psychiatric controls provided evidence of heterogeneity of MDD aetiology.”

MDD-RBD represents a subtype of MDD characterized by later onset and more severe depressive symptoms, and is associated with underlying α-synucleinopathy neurodegeneration, whereas MDD without RBD is characterized by earlier onset without apparent risk of neurodegeneration.

“Our results highlight the need to screen for RBD in psychiatric patients, especially in the MDD population, and prioritize at-risk patients for potential neuroprotective intervention to slow down or prevent future neurodegeneration,” said Professor Wing-Yun Kwok, Chairman of the Department of Psychiatry, CUHK.